title: N-Acetyltransferase 2 genetic polymorphisms and risk of colorectal cancer.
abstract: OBJECTIVE
  To investigate the possible association between meat intake, cigarette smoking and N-acetyltransferase 2 (NAT2) genetic polymorphisms on colorectal cancer (CRC) risk.
  
  
  METHODS
  Patients with CRC were matched for gender and age to healthy controls. Meat intake and cigarette smoking were assessed using a specific frequency questionnaire. DNA was extracted from peripheral blood and the genotypes of the polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism. Five NAT2 alleles were studied (WT, M1, M2, M3 and M4) using specific digestion enzymes.
  
  
  RESULTS
  A total of 147 patients with colorectal cancer (76 women and 90 men with colon cancer) and 212 controls were studied. The mean age of the two groups was 62 years. More than half the subjects (59.8% in the case group and 51.9% in the control group) were NAT2 slow acetylators. The odds ratio for colorectal cancer was 1.38 (95% CI: 0.90-2.12) in slow acetylators. Although the number of women was small (n = 76 in the case group), the cancer risk was found to be lower in intermediate (W/Mx) acetylators [odds ratio (OR): 0.55, 95% confidence interval (95% CI): 0.29-1.02]. This difference was not observed in men (OR: 0.56, 95% CI: 0.16-2.00). Among NAT2 fast acetylators (W/W or W/Mx), meat consumption more than 3 times a week increased the risk of colorectal cancer (OR: 2.05, 95% CI: 1.01-4.16). In contrast, cigarette smoking increased the risk of CRC among slow acetylators (OR: 1.97, 95% CI: 1.02-3.79).
  
  
  CONCLUSIONS
  The risk of CRC was higher among fast acetylators who reported a higher meat intake. Slow NAT2 acetylation was associated with an increased risk of CRC.
authors.affiliation: Oncology Group - Gastroenterology Division, Universidade Federal de São Paulo, 04023-900 São Paulo, Brazil.
authors.forename: Tiago Donizetti
authors.initials: TD
authors.lastname: da Silva
authors.forename: Aledson Vitor
authors.initials: AV
authors.lastname: Felipe
authors.forename: Jacqueline Miranda
authors.initials: JM
authors.lastname: de Lima
authors.forename: Celina Tizuko Fujiyama
authors.initials: CT
authors.lastname: Oshima
authors.forename: Nora Manoukian
authors.initials: NM
authors.lastname: Forones
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D004032:Diet; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008460:Meat; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D011795:Surveys and Questionnaires
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human